Seidler U, Beinborn M, Sewing K F
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Federal Republic of Germany.
Gastroenterology. 1989 Feb;96(2 Pt 1):314-20. doi: 10.1016/0016-5085(89)91553-9.
The affinities of seven natural and synthetic prostaglandins [PGE2; 16,16-dimethyl PGE2; iloprost (stable prostacyclin analogue); PGF2 alpha; PGD2; BW245c (stable PGD2 analogue); and U46619 (stable thromboxane analogue)] to the PGE2 binding site of rabbit gastric mucosa were determined by measuring [3H]PGE2 displacement from its high-affinity plasma membrane binding sites. In parallel, the potency of each prostaglandin in inhibiting acid generation in vitro was determined by measuring the inhibition of histamine-stimulated [14C]aminopyrine accumulation in rabbit parietal cells prepared by enzymatic dispersion and enriched by counterflow elutriation. All seven prostaglandins displaced [3H]PGE2 and inhibited histamine-stimulated [14C]aminopyrine accumulation in a concentration-dependent manner. For all tested prostaglandins, the IC50 values were in excellent agreement for both variables measured. It is concluded that (a) a PGE2 receptor is localized on the parietal cell and mediates inhibition of acid formation by all prostaglandins and (b) the different in vitro antisecretory potencies of prostaglandins can be attributed to their different affinities to this PGE2 receptor.
通过测量[3H]PGE2从其高亲和力质膜结合位点的置换情况，确定了七种天然和合成前列腺素[PGE2；16,16-二甲基PGE2；伊洛前列素（稳定的前列环素类似物）；PGF2α；PGD2；BW245c（稳定的PGD2类似物）；以及U46619（稳定的血栓素类似物）]与兔胃黏膜PGE2结合位点的亲和力。同时，通过测量在经酶分散制备并通过逆流淘析富集的兔壁细胞中组胺刺激的[14C]氨基比林积累的抑制情况，确定了每种前列腺素在体外抑制酸生成的效力。所有七种前列腺素均以浓度依赖性方式置换[3H]PGE2并抑制组胺刺激的[14C]氨基比林积累。对于所有测试的前列腺素，两个测量变量的IC50值高度一致。得出的结论是：(a) PGE2受体定位于壁细胞上，并介导所有前列腺素对酸形成的抑制作用；(b) 前列腺素不同的体外抗分泌效力可归因于它们对该PGE2受体的不同亲和力。
